Understanding the biological mechanisms underlying the aging process is one of the most important and urgent problems of modern biomedical science. As the demographics of the industrialized countries have changed, age-related diseases such as cancer, cardiovascular disease, stroke, osteoporosis, and Alzheimer's syndrome have taken on epidemic proportions. It is only through a thorough understanding of the aging process itself that we can begin to design rational therapeutic interventions for the alleviation of the pain of old age and its associated disorders. This proposal concerns the development and use of an animal model system for examining the relationship between gene expression and aging. Using our model system we have been able to demonstrate the existence of age-dependent gene regulation in the adult. Documentation of genes showing age-dependent regulation supports the importance of gene regulation in the aging process, confirms the existence of genetic mechanisms for its control, and provides a model system for aging which is amenable to direct genetic and molecular analysis. Through the use of our molecular biomarkers and a combination of new and traditional molecular genetic approaches we will be able to identify and isolate genetic elements that are important in setting up and controlling gene expression during the aging process.